宫颈癌
亚型
医学
蛋白质组学
多路复用
癌症
宫颈上皮内瘤变
定量蛋白质组学
宫颈癌
生物信息学
肿瘤科
癌症研究
生物
基因
内科学
遗传学
计算机科学
程序设计语言
作者
Yi Hao,Ming Ye,Xiaona Chen,Hongli Zhao,Ayshamgul Hasim,Xia Guo
标识
DOI:10.1186/s12935-021-01802-5
摘要
To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections.Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching serum samples were collected from 284 patients with normal control (n = 75, 26.41 %), precancerous lesions (n = 88, 30.99 %) and early stage cervical squamous carcinoma (n = 121, 42.61 %). HPV subtyping and quantification was performed by PCR and hybridization. 20 candidate proteins identified in previous screening studies (tissue, plasma, cells) were quantified by ELISA. Finally, highly quantitative parallel reaction monitoring mass spectrometry was used to assess the specificities and sensitivities of candidate serum markers.While CC was found to be associated with high-risk HPV subtypes, serum antibodies for high risk HPV were not significantly related to the progression of cervical cancer. Significant differences between patient groups were detected for the four proteins CLU, APOA4, APOE and MLH3, but none would allow clinical application due to insufficient sensitivity and specificity and large variability. Subsequent proteomic secretome analysis of cervical cancer cell lines identified a set of 729 common proteins. Cross referencing this dataset with ELISA measurements revealed six candidate proteins of which two, FBLN1 and ANT3, showed co-occurrence with HPV infection (75.7 % and 85 %, respectively) and had promising diagnostic ability in terms of sensitivity and specificity. After the loss of E6/E7 by using CRISPR/Cas9 gene editing, the content of ANT3 and FBLN1 in KoE6/E7 SiHa were downregulated, which indicated the expression of ANT3 and FBLN1 in cervical cancer may be affected by HPV infection.FBLN1 and ANT3 might be potential tumor- and HPV-associated serum markers.
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